Mandrel for supporting a stent and a method of using the mandrel to coat a stent

ABSTRACT

A mandrel for supporting a stent and a method of applying a coating to the stent supported by the mandrel are disclosed.

BACKGROUND OF THE INVENTION

1. Field of the Invention

This invention relates to a mandrel for supporting a stent and a methodof applying a coating to the stent supported by the mandrel.

2. Description of the Background

Blood vessel occlusions are commonly treated by mechanically enhancingblood flow in the affected vessels, such as by employing a stent. Stentsact as scaffoldings, functioning to physically hold open and, ifdesired, to expand the wall of the passageway. Typically stents arecapable of being compressed, so that they can be inserted through smalllumens via catheters, and then expanded to a larger diameter once theyare at the desired location. Examples in the patent literaturedisclosing stents include U.S. Pat. No. 4,733,665 issued to Palmaz, U.S.Pat. No. 4,800,882 issued to Gianturco, and U.S. Pat. No. 4,886,062issued to Wiktor.

FIG. 1 illustrates a conventional stent 10 formed from a plurality ofstruts 12. The plurality of struts 12 are radially expandable andinterconnected by connecting elements 14 that are disposed betweenadjacent struts 12, leaving lateral openings or gaps 16 between adjacentstruts 12. Struts 12 and connecting elements 14 define a tubular stentbody having an outer, tissue-contacting surface and an inner surface.

Stents are used not only for mechanical intervention but also asvehicles for providing biological therapy. Biological therapy can beachieved by medicating the stents. Medicated stents provide for thelocal administration of a therapeutic substance at the diseased site.Local delivery of a therapeutic substance is a preferred method oftreatment because the substance is concentrated at a specific site andthus smaller total levels of medication can be administered incomparison to systemic dosages that often produce adverse or even toxicside effects for the patient.

One method of medicating a stent involves the use of a polymeric carriercoated onto the surface of the stent. A composition including a solvent,a polymer dissolved in the solvent, and a therapeutic substancedispersed in the blend is applied to the stent by immersing the stent inthe composition or by spraying the composition onto the stent. Thesolvent is allowed to evaporate, leaving on the stent strut surfaces acoating of the polymer and the therapeutic substance impregnated in thepolymer.

A shortcoming of the above-described method of medicating a stent is thepotential for coating defects. While some coating defects can beminimized by adjusting the coating parameters, other defects occur dueto the nature of the interface between the stent and the apparatus onwhich the stent is supported during the coating process. A high degreeof surface contact between the stent and the supporting apparatus canprovide regions in which the liquid composition can flow, wick, andcollect as the composition is applied. As the solvent evaporates, theexcess composition hardens to form excess coating at and around thecontact points between the stent and the supporting apparatus. Upon theremoval of the coated stent from the supporting apparatus, the excesscoating may stick to the apparatus, thereby removing some of the neededcoating from the stent and leaving bare areas. Alternatively, the excesscoating may stick to the stent, thereby leaving excess coating as clumpsor pools on the struts or webbing between the struts.

Thus, it is desirable to minimize the interface between the stent andthe apparatus supporting the stent during the coating process tominimize coating defects. Accordingly, the present invention providesfor a device for supporting a stent during the coating applicationprocess. The invention also provides for a method of coating the stentsupported by the device.

SUMMARY OF THE INVENTION

The present invention provides a mandrel for supporting a stent. Themandrel includes a body for extending at least partially into a hollowstent for supporting the stent during the process of coating the stent.The body has a first section of a first size and a second section of asecond size, the second size being greater than the first size. The bodycan be attached to a motor for providing rotational motion.

In one embodiment, the first section is longer than the second section.In another embodiment, the first section does not make contact with theinner surface of the stent. In still another embodiment, the second sizeincludes a diameter that is less than the inner diameter of the stent.

Also provided is a device for supporting a stent. The device includes amandrel capable of extending at least partially through a hollow body ofa stent and a gear supported by the mandrel for rotating the stentduring the process of coating the stent. The gear can include teeth. Thegear can also include a textured or roughened surface.

In one embodiment, the positioning of the gear on the mandrel can beadjusted. In another embodiment, the diameter of the gear is greaterthan the diameter of the mandrel, and the diameter of the gear is lessthan the inner diameter of the stent. Accordingly, the outer surface ofthe mandrel does not contact the inner surface of the stent.

The present invention also provides a method of coating a stent. Themethod includes positioning a stent on a mandrel having a gear member.The method additionally includes rotating the mandrel to cause the gearmember to provide rotational motion to the stent and applying a coatingmaterial to the stent. In one embodiment, the act of applying includesspraying a composition including a polymer added to a fluid andoptionally an active agent added thereto onto the stent.

DESCRIPTION OF THE FIGURES

FIG. 1 illustrates a conventional stent.

FIG. 2A illustrates a mounting assembly for supporting a stent.

FIG. 2B illustrates an expanded view of the mounting assembly inaccordance with one embodiment of the present invention.

FIGS. 3A and 3B are perspective views of the gear members of themounting assembly in accordance with various embodiments of the presentinvention.

FIG. 4 is an end view of the interface between the mounting assembly andthe stent in accordance with one embodiment of the present invention.

FIG. 5 is a cross-sectional view of the interface between the mountingassembly and the stent in accordance with one embodiment of the presentinvention.

DETAILED DESCRIPTION Embodiments of the Mounting Assembly

Various types of coating defects can arise due to permanent contactpoints between a stent and its supporting apparatus. The presentinvention minimizes or eliminates such coating defects by having nopermanent contact points between a stent and its supporting apparatusduring the coating process.

Referring to FIG. 2A, a mounting assembly 18 for supporting stent 10 isillustrated to include a rod or mandrel 20 and gear members 22. Mandrel20 can connect to a motor 24, which provides rotational motion tomandrel 20, as depicted by arrow 26, during the coating process. Anothermotor 28 can also be provided for moving mandrel 20 and thus stent 10 ina linear direction, back and forth, along a rail 30.

Mandrel 20 is illustrated as having two regions with a larger diameter.The two regions can be gear members 22 for applying a torque to stent10. In commercially useful embodiments, any number of gear members 22can be used to adequately support stent 10, and the embodiments of thepresent invention should not be limited to a mandrel 20 having merelytwo gear members 22 as illustrated in the Figures. Gear members 22should be sized larger than the outer diameter of mandrel 20 so as toprevent mandrel 20 from being in contact with the inner surface of stent10. Additionally, gear members 22 should be sized smaller than the innerdiameter of stent 10 so as to provide for minimum contact between gearmembers 22 and the inner surface of stent 10. Providing gear members 22of small diameter, as compared to the inner diameter of stent 10,offsets an axis x_(M), about which gear members 22 rotate, away from anaxis x_(S), about which stent 10 rotates—axis x_(S) being positionedlongitudinally through the center of stent 10. Exemplary specificationsthat can be employed with stent 10 having a length of about 18 mm and aninner diameter of about 1.8 mm include:

Component Length (mm) Diameter (mm) Mandrel 40 0.38 Gear member 1.5 0.9

In accordance with one embodiment, gear members 22 can be permanentlyaffixed to mandrel 20. Alternatively, gear members 22 can be adjustablycoupled to mandrel 20. As illustrated in FIG. 2B, in such an embodiment,gear members 22 can include bores 32 for receiving mandrel 20. Bores 32can extend completely through gear members 22. By way of example,mandrel 20 and bores 32 can be threaded such that the clockwise orcounterclockwise rotation of gear members 22 would allow the user toadjust the location of gear members 22 along mandrel 20 to most suitablysupport stent 10.

The body of gear members 22 can be of any suitable shape. For example,gear members 22 can be without teeth, as illustrated in FIG. 3A, or caninclude teeth 34, as illustrated in FIG. 3B. The number, size, andspacing of teeth 34 can be selected to coordinate with the type of stent10 employed. In addition, the outer surface of gear members 22 can betextured or roughened for creating suitable friction against the innersurface of stent 10. However, the texture of the outer surface of gearmembers 22 should not be so rough or jagged as to cause any damage tothe inner surface of stent 10.

FIG. 4 illustrates the contact interface between gear member 22 andstent 10. Gear member 22 is in minimum contact with stent 10. Moreover,the revolution of stent 10 about gear member 22 allows the contactpoints between stent 10 and mounting assembly 18 to be transient ratherthan permanent, thereby preventing the coating material from flowing,wicking, collecting, and solidifying at or between gear member 22 andstent 10.

FIG. 5 is a cross-sectional view of the interface between stent 10 andmounting assembly 18. In one embodiment, optional barrier members 36 canbe employed so as to prevent stent 10 from sliding off of mountingassembly 18. Barrier members 36 can be spaced at a distance from stent10 so as to prevent collection of coating material between barriermembers 36 and the ends of stent 10. At least one barrier member 36should be disengagable from mandrel 20 so as to allow mounting anddismounting of stent 10.

Coating a Stent Using the Mounting Assembly

The following method of application is being provided by way ofillustration and is not intended to limit the embodiments of mountingassembly 18 of the present invention. A spray apparatus, such as EFD780S spray device with VALVEMATE 7040 control system (manufactured byEFD Inc., East Providence, R.I.), can be used to apply a composition toa stent. EFD 780S spray device is an air-assisted external mixingatomizer. The composition is atomized into small droplets by air anduniformly applied to the stent surfaces. The atomization pressure can bemaintained at a range of about 5 psi to about 20 psi. The droplet sizedepends on such factors as viscosity of the solution, surface tension ofthe solvent, and atomization pressure. Other types of spray applicators,including air-assisted internal mixing atomizers and ultrasonicapplicators, can also be used for the application of the composition.

During the application, of the composition, mandrel 20 can be rotatedabout its own central longitudinal axis. Rotation of mandrel 20 can befrom about 10 rpm to about 300 rpm, more narrowly from about 40 rpm toabout 240 rpm. By way of example, mandrel 20 can rotate at about 100rpm. Mandrel 20 can also be moved in a linear direction along the sameaxis. Mandrel 20 can be moved at about 1 mm/second to about 6 mm/second,for example about 3 mm/second, or for a minimum of at least two passes(i.e., back and forth past the spray nozzle). The flow rate of thesolution from the spray nozzle can be from about 0.01 mg/second to about1.0 mg/second, more narrowly about 0.1 mg/second. Multiple repetitionsfor applying the composition can be performed, wherein each repetitioncan be, for example, about 1 second to about 10 seconds in duration. Theamount of coating applied by each repetition can be about 0.1micrograms/cm² (of stent surface) to about 40 micrograms/cm², forexample less than about 2 micrograms/cm² per 5-second spray.

Each repetition can be followed by removal of a significant amount ofthe solvent(s). Depending on the volatility of the particular solventemployed, the solvent can evaporate essentially upon contact with thestent. Alternatively, removal of the solvent can be induced by bakingthe stent in an oven at a mild temperature (e.g., 60° C.) for a suitableduration of time (e.g., 2-4 hours) or by the application of warm air.The application of warm air between each repetition prevents coatingdefects and minimizes interaction between the active agent and thesolvent. The temperature of the warm air can be from about 30° C. toabout 60° C., more narrowly from about 40° C. to about 50° C. The flowrate of the warm air can be from about 20 cubic feet/minute (CFM) (0.57cubic meters/minute (CMM)) to about 80 CFM (2.27 CMM), more narrowlyabout 30 CFM (0.85 CMM) to about 40 CFM (1.13 CMM). The warm air can beapplied for about 3 seconds to about 60 seconds, more narrowly for about10 seconds to about 20 seconds. By way of example, warm air applicationscan be performed at a temperature of about 50° C., at a flow rate ofabout 40 CFM, and for about 10 seconds. Any suitable number ofrepetitions of applying the composition followed by removing thesolvent(s) can be performed to form a coating of a desired thickness orweight. Excessive application of the polymer in a single applicationcan, however, cause coating defects.

Operations such as wiping, centrifugation, or other web clearing actscan also be performed to achieve a more uniform coating. Briefly, wipingrefers to the physical removal of excess coating from the surface of thestent; and centrifugation refers to rapid rotation of the stent about anaxis of rotation. The excess coating can also be vacuumed off of thesurface of the stent.

In accordance with one embodiment, the stent can be at least partiallypre-expanded prior to the application of the composition. For example,the stent can be radially expanded about 20% to about 60%, more narrowlyabout 27% to about 55%—the measurement being taken from the stent'sinner diameter at an expanded position as compared to the inner diameterat the unexpanded position. The expansion of the stent, for increasingthe interspace between the stent struts during the application of thecomposition, can further prevent “cob web” formation between the stentstruts.

In accordance with one embodiment, the composition can include a solventand a polymer dissolved in the solvent. The composition can also includeactive agents, radiopaque elements, or radioactive isotopes.Representative examples of polymers that can be used to coat a stentinclude ethylene vinyl alcohol copolymer (commonly known by the genericname EVOH or by the trade name EVAL), poly(hydroxyvalerate);poly(L-lactic acid); polycaprolactone; poly(lactide-co-glycolide);poly(hydroxybutyrate); poly(hydroxybutyrate-co-valerate); polydioxanone;polyorthoester; polyanhydride; poly(glycolic acid); poly(D,L-lacticacid); poly(glycolic acid-co-trimethylene carbonate); polyphosphoester;polyphosphoester urethane; poly(amino acids); cyanoacrylates;poly(trimethylene carbonate); poly(iminocarbonate); copoly(ether-esters)(e.g. PEO/PLA); polyalkylene oxalates; polyphosphazenes; biomolecules,such as fibrin, fibrinogen, cellulose, starch, collagen and hyaluronicacid; polyurethanes; silicones; polyesters; polyolefins; polyisobutyleneand ethylene-alphaolefin copolymers; acrylic polymers and copolymers;vinyl halide polymers and copolymers, such as polyvinyl chloride;polyvinyl ethers, such as polyvinyl methyl ether; polyvinylidenehalides, such as polyvinylidene fluoride and polyvinylidene chloride;polyacrylonitrile; polyvinyl ketones; polyvinyl aromatics, such aspolystyrene; polyvinyl esters, such as polyvinyl acetate; copolymers ofvinyl monomers with each other and olefins, such as ethylene-methylmethacrylate copolymers, acrylonitrile-styrene copolymers, ABS resins,and ethylene-vinyl acetate copolymers; polyamides, such as Nylon 66 andpolycaprolactam; alkyd resins; polycarbonates; polyoxymethylenes;polyimides; polyethers; epoxy resins; polyurethanes; rayon;rayon-triacetate; cellulose; cellulose acetate; cellulose butyrate;cellulose acetate butyrate; cellophane; cellulose nitrate; cellulosepropionate; cellulose ethers; and carboxymethyl cellulose.

“Solvent” is defined as a liquid substance or composition that iscompatible with the polymer and is capable of dissolving the polymer atthe concentration desired in the composition. Examples of solventsinclude, but are not limited to, dimethylsulfoxide (DMSO), chloroform,acetone, water (buffered saline), xylene, methanol, ethanol, 1-propanol,tetrahydrofuran, 1-butanone, dimethylformamide, dimethylacetamide,cyclohexanone, ethyl acetate, methylethylketone, propylene glycolmonomethylether, isopropanol, isopropanol admixed with water, N-methylpyrrolidinone, toluene, and combinations thereof.

The active agent can be for inhibiting the activity of vascular smoothmuscle cells. More specifically, the active agent can be aimed atinhibiting abnormal or inappropriate migration and/or proliferation ofsmooth muscle cells for the inhibition of restenosis. The active agentcan also include any substance capable of exerting a therapeutic orprophylactic effect in the practice of the present invention. Forexample, the agent can be for enhancing wound healing in a vascular siteor improving the structural and elastic properties of the vascular site.Examples of agents include antiproliferative substances such asactinomycin D, or derivatives and analogs thereof (manufactured bySigma-Aldrich 1001 West Saint Paul Avenue, Milwaukee, Wis. 53233; orCOSMEGEN available from Merck). Synonyms of actinomycin D includedactinomycin, actinomycin IV, actinomycin I₁, actinomycin X₁, andactinomycin C₁. The active agent can also fall under the genus ofantineoplastic, antiinflammatory, antiplatelet, anticoagulant,antifibrin, antithrombin, antimitotic, antibiotic, antiallergic andantioxidant substances. Examples of such antineoplastics and/orantimitotics include paclitaxel (e.g. TAXOL® by Bristol-Myers SquibbCo., Stamford, Conn.), docetaxel (e.g. Taxotere®, from Aventis S. A.,Frankfurt, Germany) methotrexate, azathioprine, vincristine,vinblastine, fluorouracil, doxorubicin hydrochloride (e.g. Adriamycin®from Pharmacia & Upjohn, Peapack N.J.), and mitomycin (e.g. Mutamycin®from Bristol-Myers Squibb Co., Stamford, Conn.). Examples of suchantiplatelets, anticoagulants, antifibrin, and antithrombins includesodium heparin, low molecular weight heparins, heparinoids, hirudin,argatroban, forskolin, vapiprost, prostacyclin and prostacyclinanalogues, dextran, D-phe-pro-arg-chloromethylketone (syntheticantithrombin), dipyridamole, glycoprotein IIb/IIIa platelet membranereceptor antagonist antibody, recombinant hirudin, and thrombininhibitors such as Angiomax™ (Biogen, Inc., Cambridge, Mass.). Examplesof such cytostatic or antiproliferative agents include angiopeptin,angiotensin converting enzyme inhibitors such as captopril (e.g.Capoten® and Capozide® from Bristol-Myers Squibb Co., Stamford, Conn.),cilazapril or lisinopril (e.g. Prinivil® and Prinzide® from Merck & Co.,Inc., Whitehouse Station, N.J.); calcium channel blockers (such asnifedipine), colchicine, fibroblast growth factor (FGF) antagonists,fish oil (omega 3-fatty acid), histamine antagonists, lovastatin (aninhibitor of HMG-CoA reductase, a cholesterol lowering drug, brand nameMevacor® from Merck & Co., Inc., Whitehouse Station, N.J.), monoclonalantibodies (such as those specific for Platelet-Derived Growth Factor(PDGF) receptors), nitroprusside, phosphodiesterase inhibitors,prostaglandin inhibitors, suramin, serotonin blockers, steroids,thioprotease inhibitors, triazolopyrimidine (a PDGF antagonist), andnitric oxide. An example of an antiallergic agent is permirolastpotassium. Other therapeutic substances or agents which may beappropriate include alpha-interferon, genetically engineered epithelialcells, rapamycin and dexamethasone. Exposure of the active ingredient tothe composition should not adversely alter the active ingredient'scomposition or characteristic. Accordingly, the particular activeingredient is selected for compatibility with the solvent or blendedpolymer-solvent.

Examples of radiopaque elements include, but are not limited to, gold,tantalum, and platinum. An example of a radioactive isotope is P³².Sufficient amounts of such substances may be dispersed in thecomposition such that the substances are not present in the compositionas agglomerates or flocs.

While particular embodiments of the present invention have been shownand described, it will be obvious to those skilled in the art thatchanges and modifications can be made without departing from thisinvention in its broader aspects. Therefore, the appended claims are toencompass within their scope all such changes and modifications as fallwithin the true spirit and scope of this invention.

What is claimed is:
 1. A device for supporting a stent, comprising: amandrel capable of extending through a hollow body of a stent andattachable to a rotating apparatus; and a gear supported by the mandrel,the gear having a diameter greater than a diameter of the mandrel andpositioned on the mandrel to support the stent on an inner surface ofthe stent and to provide sufficient torque to the stent for rotating thestent during a coating process, wherein the gear includes a textured orroughened surface.
 2. The device of claim 1, wherein the positioning ofthe gear on the mandrel can be adjusted.
 3. The device of claim 1,wherein the diameter of the gear is less than an inner diameter of thestent.
 4. The device of claim 1, wherein an outer surface of the mandreldoes not contact the inner surface of the stent.
 5. A device forsupporting a stent, comprising: a mandrel capable of extending through ahollow body of a stent and attachable to a rotating apparatus; and agear supported by the mandrel, the gear having a diameter greater than adiameter of the mandrel and positioned on the mandrel to support thestent on an inner surface of the stent and to provide sufficient torqueto the stent for rotating the stent during a coating process, whereinthe gear includes teeth.
 6. A device for supporting a stent, comprising:a mandrel capable of extending through a hollow body of a stent andattachable to a rotating apparatus; and a gear supported by the mandrel,the gear having a diameter greater than a diameter of the mandrel andpositioned on the mandrel to support the stent on an inner surface ofthe stent and to provide sufficient torque to the stent for rotating thestent during a coating process, wherein the stent comprises struts andgaps disposed in between the struts, and wherein the gear includes teethsized to fit into the gaps of the stent.
 7. A longitudinal mountingdevice for rotating a stent during a coating process, comprising: amandrel having a first end and a second end and attachable to a rotatingapparatus; and a gear located between the first and second ends, thegear configured to allow a stent to rest thereon so as to form a contactarea between an outer surface of the gear and an inner surface of thestent, wherein a shape or diameter of the gear is configured so that thecontact area changes location as the stent is rotated.
 8. The mountingdevice of claim 7, further comprising a second gear between the firstand second ends of the mandrel, wherein the second gear is configured toallow the stent to rest thereon.
 9. The mounting device of claim 7,wherein the gear is substantially circular along an outer circumferenceof the gear.
 10. The mounting device of claim 7, wherein the gear hasteeth.
 11. The mounting device of claim 7, wherein the gear is removablyattached to the mandrel.
 12. The mounting device of claim 7, wherein thegear is star-shaped.
 13. A mandrel for supporting a stent during acoating process that includes rotating the stent, the mandrel comprisinga body extending through a hollow stent, wherein the body includes atextured or roughed surface area for the stent to rest thereon forcreating friction against an inner surface of the stent therebyconfigured to apply torque to the stent as the mandrel is rotated.
 14. Adevice for supporting a stent, comprising: a mandrel extending through ahollow body of a stent; and a gear supported by the mandrel andpositioned to support an inner surface of the stent during a coatingprocess, wherein the gear has a threaded bore to allow the gear to beadjustable along a length of the mandrel.